The main purpose of this proposal is to evaluate the efficacy and safety of a novel food supplement - ACAPHA, in former smokers with bronchial intraepithelial neoplasia (IEN) in a doubleblind, randomized, placebo controlled clinical trial. Bronchial IEN is defined as lesions with a nuclear morphometry index greater than 1.36 and a histopathology grade of metaplasia/worse. 2088 former smokers (greater than or equal to 30 pack-years) will be screened with image analysis of sputum cells over a three year period. Ninety subjects with one or more IEN lesions autofluorescence bronchoscopy and biopsy will receive ACAPHA/Placebo for 6 months. The unique features of this proposal are: (1) an experienced clinical trial team with a proven track record of completing several consecutive NCI sponsored chemoprevention trials on schedule, (2) a unique sputum induction method combining high frequency chest wall oscillation and 3% saline nebulization that can reduce unsatisfactory sputum samples rate to less than 3%, (3) a sputum cell image analysis method that can reduce the number of unproductive bronchoscopies by over 50%, (4) a newly developed quantitative autofluorescence bronchoscopy method that can localize IEN lesions with high sensitivity as well as to measure their size, (5) enrollment of subjects with large IEN lesions to reduce the false regression rate on re-biopsy after treatment, (6) a novel chemopreventive agent that is a food supplement with remarkable efficacy and demonstrated safety for more than 26 years, (7) the use of an electronic database of bronchial biopsy images to aid consensus diagnoses and evaluation of responses, (8) the addition of nuclear morphometry as an adjunct to histopathology in bronchial biopsies as the primary endpoint for efficacy assessment, (9) a major new initiative to develop confocal microendoscopy as a non-biopsy method to assess the effect of chemopreventive agents, and (10) testing of novel biomarkers approaches such as quantitative methylation in sputa and BAL cells. The results will provide new information on the efficacy and safety of a novel botanical food supplement for chemoprevention of lung cancer. It will also provide new information on the use of novel biomarkers as surrogate endpoints for assessing the effect of chemoprevention.